Demet Menekşe Gerede
Department of Cardiology, Faculty of Medicine, Ankara University, Ankara-Turkey
Address for Correspondence: Dr. Demet Menekşe Gerede Ankara Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı Cebeci Kalp Merkezi, Cebeci 06590, Ankara-Türkiye Phone: +90 312 595 62 86 Fax: +90 312 363 22 89 E-mail: drmeneksegerede@yahoo.com
To the Editor,
We read with a great interest the paper by Argun et al. (1) entitled “Cardioprotective effect of metformin against doxorubi-cin cardiotoxicity in rats’’ published in the Anatolian Journal of Cardiology 2015 as Epub ahead of print. The authors aimed to investigate the effectivity of metformin in doxorubicin-induced cardiotoxicity using cardiac markers in blood and histopatholog-ical examination in the rat model. They concluded that metformin improved the left ventricular function, histopathologic change, and cardiomyocyte apoptosis. We congratulate the authors for this valuable investigation, and we have a few comments.
Doxorubicin (DXR) is a very effective and commonly used chemotherapeutic drug for the treatment of different types of cancers. It blocks cell division and growth by interacting DNA and RNA formation. However, it can cause a life-threatening heart damage, resulting in left ventricular dysfunction, thus limit-ing its usage (2).
Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are useful predictors of decreased left ventricular function in patients treated with DXR. ANP secretion from atria is triggered by atrial dilatation due to cardiac or noncardiac rea-sons. BNP is produced in the ventricle and is more specific for heart failure than ANP (1–3). Koh et al. (3) reported that plasma BNP levels significantly increased from 6 to 12 weeks in the doxorubicin-induced cardiotoxicity. In the study by Argun et al. (1), there was no statistical difference among groups in terms of ANP or BNP. This may be due to the design of the study, which is relatively short for the occurrence of chronic heart failure be-cause of DXR.
Cardiac troponin (TnT) is a very specific and highly sensi-tive marker for myocardial damage and commonly used in clini-cal practice. Similar to BNP, TnT has been reported as an inde-pendent predictor of cardiac mortality in heart failure (2–4). In the study by Argun et al. (1), it would have been very helpful to measure TnT levels in terms of myocardial injury due to DXR. Thus, one could make an interpretation that TnT levels had
in-creased in the early stage in the DXR-induced cardiotoxicity, but no change were observed in the BNP levels, which is very cru-cial for the early detection of DXR-induced cardiotoxicity before irreversible damage.
Mustafa Gülgün, Kürşat Fidancı, Fatih Alparslan Genç, Vural Kesik* Departments of Pediatric Cardiology and *Pediatric Oncology, Gülhane Military Medical Academy, Ankara-Turkey
References
1. Argun M, Üzüm K, Sönmez MF, Özyurt A, Karabulut D, Soyersarıca Z, et al. Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats. Anatol J Cardiol 2015 Apr 30. Epub ahead of print.
2. Kesik V, Yüksel R, Yiğit N, Saldır M, Karabacak E, Erdem G, et al. Ozone Ameliorates Doxorubicine-Induced Skin Necrosis - results from an animal model. Int J Low Extrem Wounds 2015 Aug 18. Epub ahead of print.
3. Koh E, Nakamura T, Takahashi H. Troponin-T and brain natriuretic peptide as predictors for adriamycin-induced cardiomyopathy in rats. Circ J 2004; 68: 163-7. [CrossRef]
4. Nakamura Y, Yoshihisa A, Takiguchi M, Shimizu T, Yamauchi H, Iwa-ya S, et al. High-sensitivity cardiac troponin T predicts non-cardiac mortality in heart failure. Circ J 2014; 78: 890-5. [CrossRef]
Address for Correspondence: Dr. Mustafa Gülgün GATA, Pediyatrik Kardiyoloji Bölümü,
06010 Etlik, Ankara-Türkiye Phone: +90 312 304 18 92
E-mail: mustafagulgun@yahoo.com, mgulgun@gata.edu.tr ©Copyright 2016 by Turkish Society of Cardiology - Available online at www.anatoljcardiol.com
DOI:10.14744/AnatolJCardiol.2016.7001
Author`s Reply
To the Editor,
Many thanks to the authors for their important comments to our paper entitled “Cardioprotective effect of metformin against doxorubicin cardiotoxicity in rats” published in the Anatolian Journal of Cardiology 2015 as Epub ahead of print (1). It is of great importance to detect cardiotoxicity as early as possible in patients receiving cardiotoxic chemotherapy. This would make it possible to minimize cardiotoxicity-associated mortality and morbidity.
The role of cardiac biomarkers such as cardiac troponins and natriuretic peptides in the prediction of chemotherapy-in-duced cardiotoxicity has been investigated in animal models and clinical studies. These studies have focused on the early detec-tion of cardiotoxicity and/or the relative sensitivities of the avail-able biomarkers for the prediction of cardiotoxicity.
As you indicated, our study could have achieved more sig-nificant results if troponins had also been studied in conjunction with brain natriuretic peptide (BNP). Although some studies have not reported significant chemotherapy-induced elevations in
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